Three-drug regimen provides rapid, durable responses for multiple myeloma

In continuation of my update on three drug combination

A three-drug treatment for the blood cancer multiple myeloma provided rapid, deep and potentially durable responses, researchers report today online in Blood, the Journal of the American Society of Hematology, and yesterday, Sunday, June 3, 2012, at the American Society of Clinical Oncology's Annual Meeting in Chicago, IL, USA.

The researchers, led by Andrzej J. Jakubowiak, MD, PhD, professor of medicine and director of the multiple myeloma program at the University of Chicago Medical Center, found that combining carfilzomib, a next generation proteasome inhibitor, with two standard drugs -- lenalidomide and low-dose dexamethasone compared favorably to other frontline regimens.
The longer patients stayed on the therapy, the better their response. After at least eight 28-day cycles of treatment, 61 percent of the 36 patients who remained on the therapy had a stringent complete response, defined as no detectable tumor cells or myeloma protein in the blood or bone marrow; 78 percent had at least a near complete response. More than 90 percent of patients had no progression of their disease at two years.

"These rapid and durable response rates are higher than those achieved by the best established regimens for newly diagnosed multiple myeloma," said Jakubowiak. "We have observed excellent efficacy, the best reported to date, and very good tolerability, including limited peripheral neuropathy that has been problematic with other drug combinations."

 Ref : http://www.uchospitals.edu/news/2012/20120604-myeloma.html

 Three-drug regimen provides rapid, durable responses for multiple myeloma

HIV drug may slow down metastatic breast cancer

The HIV drugs known as CCR5 antagonists (Maraviroc or Vicriviroc see below structures from left to right respectively) may also help prevent aggressive breast cancers from metastasizing, researchers from the Kimmel Cancer Center at Jefferson suggest in a preclinical study. 

Such drugs target the HIV receptor CCR5, which the virus uses to enter and infect host cells, and has historically only been associated with expression in inflammatory cells in the immune system. Researchers have now shown, however, that CCR5 is also expressed in breast cancer cells, and regulates the spread to other tissue.

What's more, blocking the receptor with the CCR5 antagonists Maraviroc and Vicriviroc, two drugs that slow down the spread of the HIV virus by targeting the CCR5 co-receptor of the chemokine CCL5, also prevents migration and spread of basal breast cancer cells, the researchers found.

"These results are dramatic," said Richard Pestell, M.D., Ph.D., FACP, Director of Jefferson's Kimmel Cancer Center and Chair of the Department of Cancer Biology at Thomas Jefferson University, and study senior author. "Our team showed that the CCR5/CCL5 axis plays a key role in invasiveness, and that a CCR5 antagonist can slow down the invasion of basal breast cancer cells."

"This suggests it may prove to be a viable adjuvant therapy to reduce the risk of metastasis in the basal breast cancer subtype," he added.

Basal tumors, which do not express the androgen or estrogen receptors or HER-2, are typically associated with metastasis and often do not respond to hormonal therapies. Current treatments include chemotherapy, radiation, and surgery, but all demonstrate poor outcomes, thus highlighting the urgent need for a specific targeted therapy for the subtype.

More : http://cancerres.aacrjournals.org/content/early/2012/05/25/0008-5472.CAN-11-3917

HIV drug may slow down metastatic breast cancer

New drug found effective against rare form of basal cell skin cancer

In continuation of my up date on vismodegib..

A clinical study has demonstrated that a new drug, a targeted molecular therapy called vismodegib (trade name Erivedge™), can dramatically shrink basal cell skin cancers and prevent the formation of new ones, in patients with basal cell nevus syndrome (BCNS). This rare genetic condition causes dozens, and sometimes hundreds or thousands, of skin cancers on each patient's body. The primary treatment option is surgical removal. These study results are significant as they indicate the possibility of an alternative treatment with oral medication; although side effects remain a consideration. 

New drug found effective against rare form of basal cell skin cancer

Kinase Inhibitor Trials Show Melanoma Benefits | News | Drug Discovery and Development Magazine

Findings from GlaxoSmithKline (GSK) plc’s Phase 3 clinical study program evaluating single agent therapy with the targeted anti-cancer agents, dabrafenib (below left structure) and trametinib (below right structure), in patients with BRAF V600 mutation positive metastatic melanoma have been released. 

Both the BREAK3 study of dabrafenib (BRAF inhibitor) and the METRIC study of trametinib (MEK inhibitor) demonstrated a statistically significant benefit in the length of time patients with BRAF V600 mutation positive advanced or metastatic melanoma lived without progression of their disease or death (Progression Free Survival or PFS) compared to those receiving chemotherapy. Additionally, patients in the METRIC study who received trametinib lived significantly longer (overall survival or OS) than those who received chemotherapy with dacarbazine. OS data are not yet mature in the BREAK3 trial.

“The results from the clinical studies of dabrafenib and trametinib presented at this meeting represent important progress towards understanding how these investigational agents could benefit patients with advanced and metastatic melanoma. Importantly, trametinib is the first MEK inhibitor to demonstrate clinical benefit in a late phase melanoma trial.” said Dr. Rafael Amado, Head of Oncology R&D for GlaxoSmithKline. “We are planning regulatory submissions for dabrafenib and trametinib as single agent therapies and have recently started a Phase 3 program to further investigate the effect of the combination in this disease.”

OGX-427 Improves PFS in Prostate Cancer | News | Drug Discovery and Development Magazine

In continuation of my update on OGX-427 

OncoGenex Pharmaceuticals Inc. announced data from a Phase 2 study of its investigational compound OGX-427 in chemotherapy-naive metastatic castration resistant prostate cancer (mCRPC) patients. Preliminary results show a higher number of patients taking OGX-427 plus prednisone without disease progression at 12 weeks and with declines in prostate-specific antigen (PSA), compared with those taking prednisone alone.

Sixty-four of 72 planned patients have been randomized to the study and data on 42 patients [22 who received OGX-427 plus prednisone and 20 who received prednisone alone] are now available at or beyond the 12 week assessment time point. Highlights are as follows: 

Phase 3 Elagolix Trial Begins | News | Drug Discovery and Development Magazine

Elagolix (see structure) is an oral gonadotropin-releasing hormone (GnRH) antagonist. "Endometriosis can be a debilitating disease that affects millions of women around the world and the exploration of new treatments could offer other options for women with this disease," said Dr. Hugh Taylor, M.D., Chief of Division of Reproductive Endocrinology and Infertility, Yale School of Medicine.

The Phase 3 trial (M12-665) is a 24-week, multinational, randomized, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of elagolix in 875 women, age 18 to 49, with moderate-to-severe endometriosis-associated pain. It will be conducted at approximately 160 sites in the United States, Puerto Rico and Canada.

"The investigation of elagolix for endometriosis is an important step in the exploration of potential treatments for this underserved patient population," said Rita Jain, M.D., divisional vice president, Pain, Respiratory and Metabolic Development, Global Pharmaceutical R&D, Abbott.

The trial has begun screening for enrollment. A second Phase 3 study is planned with an NDA filing targeted in 2016.

Phase 3 Elagolix Trial Begins | News | Drug Discovery and Development Magazine

Nicotinamide riboside can protect against obesity

A natural ingredient found in milk can protect against obesity even as mice continue to enjoy diets that are high in fat. 

The researchers identified this ingredient, known as nicotinamide riboside (see structure), as they were searching for alternative ways to boost the well-known gene SIRT1, which comes with benefits for both metabolism and longevity. One way to do that is to target SIRT1 directly, as the red wine ingredient resveratrol appears to do, at least at some doses.

Auwerx's team lead by Johan Auwerx, suspected there might be a simpler way to go about it, by boosting levels of one of SIRT1's molecular sidekicks, the cofactor NAD+. 

This milk ingredient does just that in a rather appealing way. Not only is it a natural product, but it also gets trapped within cells, where it can do its magic.

Mice that take nicotinamide riboside in fairly high doses along with their high-fat meals burn more fat and are protected from obesity. They also become better runners thanks to muscles that have greater endurance.

http://www.youtube.com/embed/5YwzyqXzntY

Nicotinamide riboside can protect against obesity

BioLineRx receives two U.S. patent allowances for BL-1021 to treat neuropathic pain

BioLineRx, a biopharmaceutical development company, announced today that two Notices of Allowance have been issued by the United States Patent and Trademark Office (USPTO) for BL-1021 (see structure), an orally available small molecule for treating neuropathic pain. The first has been issued for a patent application claiming BL-1021's composition, that when issued, will be valid until at least September 2022. Additional patents claiming BL-1021's composition are granted or pending in Europe, Japan, Canada, Korea, Mexico, Israel, India, China and Australia. The other Notice of Allowance is for a patent application claiming the use of BL-1021 for the treatment of pain, that when issued, will be valid until at least January 2028.

BioLineRx receives two U.S. patent allowances for BL-1021 to treat neuropathic pain: BioLineRx, a biopharmaceutical development company, announced today that two Notices of Allowance have been issued by the United States Patent and Trademark Office (USPTO) for BL-1021, an orally available small molecule for treating neuropathic pain.

Novel way to treat drug-resistant brain tumor cells

In continuation of my update on Lapatinib

Research by Dr. Paul Clark, a scientist in Kuo's lab and the study's lead author, shows why. When cetuximab treatment switches off EGFR activity and should inhibit cancer-cell growth, cancer stem cells compensate by turning on two other EGFR family receptors (ERBB2 and ERBB3) and continue to grow. One of these receptors, ERBB2, is implicated in certain types of chemotherapy-resistant breast cancer. Fortunately, another novel drug already approved by the FDA, lapatinib (see the structure), inhibits ERBB2 activity and signaling by multiple EGFR members.

This study shows that cancer stem-cell growth was markedly inhibited by lapatinib treatment, which results in combined knockout of multiple EGFR family members.

"This is good news, because these drugs target an important mechanism for the (GBM) cancer cells to grow so quickly and evade current therapies, and these molecularly targeted drugs are also well-tolerated by patients and have minimal side effects," Dr. Clark said.

Ref : http://www.med.wisc.edu/news-events/wisconsin-research-team-reveals-novel-way-to-treat-drug-resistant-brain-tumor-cells/37811

Novel way to treat drug-resistant brain tumor cells: New research explains why the incurable brain cancer, glioblastoma multiforme (GBM), is highly resistant to current chemotherapies.

Increased fiber intake associated with lower risk of dying over twelve year period - Life Extension Update

Fiber could promote health via several mechanisms, including helping to control weight, improving glycemic control, and aiding in the maintenance of a favorable intestinal environment. Fiber may help protect against circulatory diseases by lowering low density lipoprotein (LDL) cholesterol, which, when elevated, is a major risk factor for cardiovascular disease. Fiber intake has also been associated with a reduction in inflammatory markers including C-reactive protein, interleukin-6 and tumor necrosis factor-alpha. The authors note that greater total fiber intake could be a marker of an overall dietary pattern that benefits health.

"We observed inverse associations between total dietary fiber intake and mortality, and specifically mortality from circulatory, digestive, and non-cardiovascular disease, noncancer inflammatory diseases," the authors conclude. "These results show that high fiber intake, mainly from cereals and vegetables, may reduce the risk of death from these diseases." 

Increased fiber intake associated with lower risk of dying over twelve year period - Life Extension Update